The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is committed to improving the health of patients with rheumatic, musculoskeletal, and skin diseases by supporting investigator-initiated clinical trials that lead to better clinical outcomes. The NIAMSí goal is to identify and fund trials that are as timely and informative as possible, and that will lead to improvements in clinical practices for disease prevention, diagnosis, and treatment. To this end, the NIAMS has enhanced its clinical trials program.

The NIAMS clinical trials program is designed to support the spectrum of such studies with funding mechanisms tailored to different levels of complexity and risk. Investigators planning short-term studies that involve few subjects and limited duration of follow-up with the goal of collecting experimental data needed to launch a future clinical trial may apply for a NIAMS Exploratory Clinical Trial Planning Grant (R21) or a Clinical Observational (CO) Studies in Musculoskeletal, Rheumatic, and Skin Diseases (R01) grant. For trials involving greater numbers of subjects or of greater complexity, the NIAMS supports investigator-initiated, clinical interventional trials through a two part process: (1) a Clinical Trial Planning Grant (U34) followed by (2) a Clinical Trial Implementation Cooperative Agreement (U01) to fully implement and conduct the study. Investigators are strongly encouraged to consult with the NIAMS prior to submitting an application. NIAMS staff will consider whether the proposed clinical project meets the goals and mission of the Institute and whether it is appropriate for an investigator-initiated application, but will not evaluate the technical and scientific merit of the proposal. Technical and scientific merit will be determined during peer review. In the pre-submission consultation phase, if the proposal does not meet the goals and mission of the NIAMS, applicants will be so informed.

Investigators who anticipate submitting a Clinical Trial Planning Grant (U34) or Clinical Trial Implementation Grant application (U01) to the NIAMS Clinical Funding Opportunity Announcements (FOAs) should consider the items below in preparation for a pre-submission consultation with a NIAMS Program Officer.

Anticipated date of submission

Study title

Study PI(s)

Primary institution and potential collaborating sites

Brief description of the objectives of the clinical trial

Brief rationale for the proposed clinical trial:

Scientific basis

Clinical significance

Total cost estimate of the clinical trial (not the planning grant), by year

Estimated start date and duration of the clinical trial

For applicants intending to submit a U01 Clinical Trial Implementation (U01) grant, a separate document that summarizes each of the planning Milestones and provides a status of each task. Any tasks that remain incomplete either under an ongoing U34 planning grant or otherwise before the trial can open for recruitment must be detailed and justified.

Furthermore, investigators are strongly encouraged to notify the NIAMS prior to submission of the application for either a U34 or a U01 through a Letter of Intent (LOI). Applicants are encouraged to allow enough time before the planned receipt date to give the Institute at least 10 weeks to discuss the potential application with the investigators, particularly if there has been no prior consultation with the NIAMS about the application and/or the applicant is requesting a waiver to the U34 Clinical Trial Planning (U34) grant (see Requests for a U34 Waiver). Instructions for preparing the LOI are provided in the FOA. LOIs should be submitted to the Scientific/Research contacts listed in the FOA, who will share the request with the appropriate Program Officer.

In addition to technical merit, the NIAMS will consider program priorities in making funding decisions. Applications that do not meet the criteria outlined above or that are judged to be of low program priority will not receive funding even if found to be scientifically sound in peer review. One benefit of consultation prior to submission of an application is that the Program Officer can discuss with the investigator the extent to which the potential project fits with NIAMS program priorities.

The NIAMS reserves the right to determine that support for clinical trials may be directed through other available mechanisms supported by the NIAMS.

Applications with Direct Costs of $500,000 or Greater in Any Year

Pre-approval is required prior to submission of an application which will have direct costs of $500,000 or more in any given year, as per NIH policy (see NOT-OD-02-004). Applicants should refer to http://www.niams.nih.gov/Funding/Clinical_Research/clinical_letter_request.asp for information about what to include in their Letter of Request (LOR). Applicants should allow enough time before their planned receipt date to give the Institute at least 10 weeks to determine whether it will approve the written request to submit a U01.

Requests for a Waiver to the NIAMS U34 Planning for a Clinical Trial Implementation (U01) grant applications with direct costs of less than $500,000 in any given year

In some cases, the Clinical Trial Implementation (U01) grant can be submitted without a prior U34 planning grant if the planning tasks have been or will be accomplished through other means (e.g., a previously funded R34 grant) before implementation of the clinical trial. Applicants should consult with a NIAMS Program Director or Clinical Coordinator to determine if the NIAMS will consider a U34 waiver request. Documentation that summarizes each of the planning Milestones and provides a status and timeline of each task is required. Any tasks that remain incomplete before the trial can open for recruitment must be detailed and justified. However, please note that the NIAMS may also ascertain that substantial additional planning is necessary and not grant a waiver to the U34 requirement. Those applicants will be directed to apply to the Clinical Trial Planning Grant (U34) Cooperative Agreement FOA and delay submission of the U01.